Induction of Cellular Quinone Reductase by Some Flavonoids

Kwon, Chong-Suk;Kim, Ji-Hyun;Son, Kun-Ho;Kim, Young-Kyoon;Kim, Woo-Keun;Kim, Jong-Sang

  • Published : 20031200

Abstract

Induction of quinone reductase (QR; NAD(P)H: (quinone-acceptor) oxidoreductase), which promotes an obligatory two-electron reduction of quinones and prevents their participation in oxidative cycling and, thereby, the depletion of intracellular glutathione, has been used as a marker for chemopreventive agents. Induction of phase 2 enzymes is considered to be an important mechanism of cancer prevention. To search for novel cancer preventive agents, we assessed the QR-inducing activities of some flavonoids in cultured murine hepatoma cells. Among fifteen flavonoids tested in this study, baicalin, ginkgetin, isoginkgetin, linarin, and luteolin significantly induced QR activity in hepac1c7 cells. Ginkgetin and luteolin at the concentration of 0.5 ug/mL induced QR by 31 and 24%, respectively. Isoginkgetin and linarin induced QR in a dose-dependent manner, by 33 and 49%, respectively at the concentration of 8 ug/mL. Bilobetin, ginkgetin, and isoginkgetin induced QR in both hepa1c1c7 and its mutant BPRc1 cell lines. In short, these flavonoids with significant QR-inducing activities merit further animal and clinical studies to assess their potential as cancer preventive agents.

Keywords

References

  1. Proceedings of the National Academy of Sciences v.90 no.7 Chemical and molecular regulation of enzymes that detoxify carcinogens Prestera, T.;Holtzclaw, W.D.;Zhang, Y.S.;Talalay, P. https://doi.org/10.1073/pnas.90.7.2965
  2. Cancer Epidemiol. Biomarkers Prev. v.11 Identification of potential prostate cancer preventive agents through induction of quinone reductase in vitro Brooks, J.D.;Goldberg, M.F.;Nelson, L.A.;Wu, D.;Nelson, W.G.
  3. Proceedings of the National Academy of Sciences v.83 no.3 Induction of NAD(P)H:quinone reductase in murine hepatoma cells by phenolic antioxidants, azo dyes, and other chemoprotectors: A model system for the study of anticarcinogens De Long, M.J.;Prochaska, H.J.;Talalay, P. https://doi.org/10.1073/pnas.83.3.787
  4. Journal of Biological Chemistry v.270 no.12 ARE- and TRE-mediated regulation of gene expression; Response to xenobiotics and antioxidants Xie, T.;Belinsky, M.;Xu, Y.;Jaiswal, A.K. https://doi.org/10.1074/jbc.270.12.6894
  5. Adv. Pharmacol. v.38 Antioxidant-Inducible Genes Primiano, T.;Sutter, T.R.;Kensler, T.W.
  6. Cancer Letters v.120 no.2 Induction of the anticarcinogenic marker enzyme, quinone reductase, in murine hepatoma cells in vitro by flavonoids Uda, Y.;Price, K.R.;Williamson, G.;Rhodes, M.J. https://doi.org/10.1016/S0304-3835(97)00311-X
  7. Pharmacology & Therapeutics v.96 no.2 The biochemistry and medical significance of the flavonoids Havsteen, B.H. https://doi.org/10.1016/S0163-7258(02)00298-X
  8. Cancer Epidemiol. Biomarkers Prev. v.11 Identification of potential prostate cancer preventive agents through induction of quinone reductase in vitro Brooks, J.D.;Goldberg, M.F.;Nelson, L.A.;Wu, D.;Nelson, W.G.
  9. Journal of Agricultural and Food Chemistry v.50 no.21 Antiproliferative activities of citrus flavonoids against six human cancer cell lines Manthey, J.A.;Guthrie, N. https://doi.org/10.1021/jf020121d
  10. Cancer Res. v.48 Regulatory mechanism of monofunctional and bifunctional anti-carcinogenic enzyme inducers in murine liver Prochaska, H.;Talalay, P.
  11. Carcinogenesis v.8 no.10 Role of cytochrome P1-450 in the induction of NAD(P)H:quinone reductase in a murine hepatoma cell line and its mutants De Long, M.;Santamaria, A.;Talalay, P. https://doi.org/10.1093/carcin/8.10.1549
  12. Proceedings of the National Academy of Sciences v.77 no.9 Increase of NAD(P)H:Quinone reductase by dietary antioxdants; Possible role in protection against carcinogenesis and toxicity Benson, A.M.;Hunkeler, M.J.;Talalay, P. https://doi.org/10.1073/pnas.77.9.5216
  13. Cancer Res. v.48 Regulatory mechanisms of monofunctional and bifunctional anticarcinogenic enzyme inducers in murine liver Prochaska, H.J.;Talalay, P.
  14. J. Biol. Chem. v.193 Protein measurement with the Folin phenol reagent Lowry, O.H.;Rosebrough, N.J.;Farr, A.L.;Randall, R.J.
  15. Journal of Medicinal Chemistry v.41 no.26 Chemoprotective properties of phenylpropenoids, bis (benzylidene) cycloalkanones, and related Michael reaction acceptors: correlation of potencies as phase 2 enzyme inducers and radical scavengers Dinkova-Kostova, A.T.;Abeygunawardana, C.;Talalay, P. https://doi.org/10.1021/jm980424s
  16. Proceedings of the National Academy of Sciences v.85 no.21 Identification of a common chemical signal regulating the induction of enzymes that protect against chemical carcinogenesis Talalay, P.;De Long, M.J.;Prochaska, H.J. https://doi.org/10.1073/pnas.85.21.8261
  17. Advances in Enzyme Regulation v.33 The electrophile counterattack response: protection against neoplasia and toxicity Prestera, T.;Zhang, Y.;Spencer, S.R.;Wilczak, C.A.;Talalay, P. https://doi.org/10.1016/0065-2571(93)90024-8
  18. J. Dermatol. v.28 Effect of biflavones of Ginkgo biloba against UVB-induced cytotoxicity in vitro Kim, S.J.
  19. Planta Medica v.65 no.5 Inhibition of rat adjuvant-induced arthritis by ginkgetin, a biflavone from ginkgo biloba leaves Kim, H.K.;Son, K.H.;Chang, H.W.;Kang, S.S.;Kim, H.P. https://doi.org/10.1055/s-2006-960815
  20. Planta Medica v.68 no.4 Effects of Ginkgetin from Ginkgo biloba leaves on cyclooxygenases and in vivo skin inflammation Kwak, W.J.;Han, C.K.;Son, K.H.;Chang, H.W.;Kang, S.S.;Park, B.K.;Kim, H.P. https://doi.org/10.1055/s-2002-26742
  21. Life Sciences v.57 no.6 Suppression of mouse lymphocyte proliferation in vitro by naturally-occurring biflavonoids Lee, S.J.;Choi, J.H.;Son, K.H.;Chang, H.W.;Kang, S.S.;Kim, H.P. https://doi.org/10.1016/0024-3205(95)00305-P
  22. Oncogene v.17 no.24 Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes Venugopal, R.;Jaiswal, A.K. https://doi.org/10.1038/sj.onc.1202237
  23. J. Food Sci. Nutr. v.4 Induction of quinone reductase, an anticarcinogenic marker enzyme, by vitamin E in both hepalclc7 cells and mice Kwon, C.S.;Kim, J.S.
  24. Toxicology Letters v.119 no.1 Induction of human NAD(P)H:quinone oxidoreductase(NQO1) gene expression by the flavonol quercetin Valerio, L.G. Jr.;Kepa, J.K.;Pickwell, G.V.;Ruattrochi, L.C. https://doi.org/10.1016/S0378-4274(00)00302-7
  25. J. Nutr. v.131 Curcumin and especially tetrahydrocurcumin ameliorate oxidative stress-induced renal injury in mice Okada, K.;Wangpoengtrakul, C.;Tanaka, T.;Toyokuni, S.;Uchida, K.;Osawa, T.
  26. Biochemical Pharmacology v.60 no.2 Role of NAD(P)H:quinone oxidoreductase 1 (DT diaphorase) in protection against quinone toxicity Joseph, P.;Long, D.J.;Klein-Szanto, A.J.;Jaiswal, A.K. https://doi.org/10.1016/S0006-2952(00)00321-X